{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T17:28:09Z","timestamp":1786728489433,"version":"build-2736575974"},"reference-count":19,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T00:00:00Z","timestamp":1723075200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,1]]},"abstract":"ABSTRACT<\/jats:title>\n \n Objective:<\/jats:title>\n To investigate the molecular characteristics of Rb\/E2F in mixed adeno-neuroendocrine carcinoma (MANEC).<\/jats:p>\n <\/jats:sec>\n \n Materials and Methods:<\/jats:title>\n \n The clinicopathological features of MANEC were analyzed. The protein expressions of Rb, p16, and p53 were detected by the immunohistochemical method. The infection status of high-risk human papillomavirus (HR-HPV) was evaluated by\n in situ<\/jats:italic>\n hybridization (ISH) and the gene chip method.\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n Thirteen cases of MANEC were divided into four molecular patterns according to Rb protein expression and HPV status. Group 1: A total of eight of the 13 cases showed positive Rb protein expression and lack of HR-HPV expression (8\/13, 62%). Rb protein expression with p16 protein deletion and p53 protein abnormal expression was unique to NEC. Group 2: three cases (3\/13, 23%) with negative Rb protein expression and lack of HR-HPV expression. Group 3: There was one case (1\/13, 8%) with positive expression of Rb protein accompanied by HR-HPV. Group 4: There was one case of Rb protein loss with an HR-HPV-positive status.<\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n HR-HPV and Rb\/p16\/p53 pathway can be associated in MANEC pathogenesis, which provides the research basis for personalized treatment of MANEC.<\/jats:p>\n <\/jats:sec>","DOI":"10.4103\/ijpm.ijpm_511_23","type":"journal-article","created":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T11:12:05Z","timestamp":1723461125000},"page":"79-87","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Identification of human papillomavirus and Rb\/E2F pathway genomic alterations in mixed adeno-neuroendocrine carcinoma"],"prefix":"10.4103","volume":"68","author":[{"given":"Feng","family":"Ling","sequence":"first","affiliation":[{"name":"Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, China"},{"name":"Precision Pathology Diagnosis for Serious Diseases Key Laboratory of LuZhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihui","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, China"},{"name":"Precision Pathology Diagnosis for Serious Diseases Key Laboratory of LuZhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2024,8,8]]},"reference":[{"key":"R2-20250411","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.ejso.2023.01.005","article-title":"Management and outcomes of mixed adenoneuroendocrine carcinoma of the ampulla of Vater:A systematic review and pooled analysis of 56 patients","volume":"49","author":"Ziogas","year":"2023","journal-title":"Eur J Surg Oncol"},{"key":"R3-20250411","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1097\/PAS.0000000000001943","article-title":"Morphologic and molecular heterogeneity of cervical neuroendocrine neoplasia:A report of 14 cases","volume":"46","author":"Ordulu","year":"2022","journal-title":"Am J Surg Pathol"},{"key":"R4-20250411","doi-asserted-by":"crossref","first-page":"e50","DOI":"10.3802\/jgo.2023.34.e50","article-title":"RB1 alteration and poor prognosis in women with high-grade neuroendocrine carcinoma of the uterine cervix:A NeCTuR study","volume":"34","author":"Flores","year":"2023","journal-title":"J Gynecol Oncol"},{"key":"R5-20250411","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/nature14664","article-title":"Comprehensive genomic profiles of small cell lung cancer","volume":"5","author":"George","year":"2015","journal-title":"Nature"},{"key":"R6-20250411","first-page":"1","article-title":"Biology and evolution of poorly differentiated neuroendocrine tumors","volume":"2","author":"Rickman","year":"2017","journal-title":"Nat Med"},{"key":"R7-20250411","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1097\/01.MP.0000077417.08371.CE","article-title":"Expression of p16, Rb, and p53 proteins in squamous cell carcinomas of the anorectal region harboring human papillomavirus DNA","volume":"1","author":"Lu","year":"2003","journal-title":"Mod Pathol"},{"key":"R8-20250411","first-page":"342","article-title":"Papillomaviruses and cancer:From basic studies to clinical application","volume":"4","author":"Zur","year":"2002","journal-title":"Nat Rev Cancer"},{"key":"R9-20250411","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1097\/00000478-200211000-00001","article-title":"p16INK4a immunohistochemistry improves interobserver agreement in the diagnosis of cervical intraepithelial neoplasia","volume":"26","author":"Klaes","year":"2002","journal-title":"Am J Surg Pathol"},{"key":"R10-20250411","first-page":"1","article-title":"Mixed mucinous adenocarcinoma\/large cell neuroendocrine carcinoma of the uterine cervix:Case report and molecular characterization of a rare entity","volume":"3","author":"Fattorini","year":"2023","journal-title":"Virchows Arch"},{"key":"R11-20250411","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.ejca.2023.03.024","article-title":"Molecular profiling and target actionability for precision medicine in neuroendocrine neoplasms:real-world data","volume":"186","author":"Boil\u00e8ve","year":"2023","journal-title":"Eur J Cancer"},{"key":"R12-20250411","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1158\/2159-8290.CD-22-0620","article-title":"Integrative analysis of a large real-world cohort of small cell lung cancer identifies distinct genetic subtypes and insights into histological transformation","volume":"7","author":"Sivakumar","year":"2023","journal-title":"Cancer Discov"},{"key":"R13-20250411","doi-asserted-by":"crossref","first-page":"100964","DOI":"10.1016\/j.jbior.2023.100964","article-title":"Targeted pharmacologic inhibition of S-phase kinase-associated protein 2 (SKP2) mediated cell cycle regulation in lung and other RB-Related cancers:A brief review of current status and future prospects","volume":"88","author":"Elahi","year":"2023","journal-title":"Adv Biol Regul"},{"key":"R14-20250411","doi-asserted-by":"crossref","first-page":"1093332","DOI":"10.3389\/fendo.2023.1093332","article-title":"ZBTB7A as a novel vulnerability in neuroendocrine prostate cancer","volume":"14","author":"Bae","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"key":"R15-20250411","doi-asserted-by":"crossref","first-page":"5220","DOI":"10.1038\/sj.onc.1209615","article-title":"RB and cell cycle progression","volume":"2","author":"Giacinti","year":"2006","journal-title":"Oncogene"},{"key":"R16-20250411","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.semcancer.2023.03.004","article-title":"Role of E2F transcription factor in oral cancer:Recent insight and advancements","volume":"92","author":"Kassab","year":"2023","journal-title":"Semin Cancer Biol"},{"key":"R17-20250411","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1111\/pin.12569","article-title":"A case of rectal neuroendocrine carcinoma in a patient with long-standing ulcerative colitis involving alterations of the p16-Rb pathway","volume":"67","author":"Tomoko","year":"2017","journal-title":"Pathol Int"},{"key":"R18-20250411","first-page":"4620","article-title":"E7 protein of human papilloma virus-16 induces degradation of retinoblastoma protein through the ubiquitin-proteasome pathway","volume":"5","author":"Boyer","year":"1996","journal-title":"Cancer Res"},{"key":"R19-20250411","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/0092-8674(90)90409-8","article-title":"The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53","volume":"6","author":"Scheffner","year":"1990","journal-title":"Cell"},{"key":"R20-20250411","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/s41379-018-0131-6","article-title":"Identification of high-risk human papillomavirus and Rb\/E2F pathway genomic alterations in mutually exclusive subsets of colorectal neuroendocrine carcinoma","volume":"32","author":"Shamir","year":"2019","journal-title":"Mod Pathol"}],"container-title":["Indian Journal of Pathology and Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/ijpm.ijpm_511_23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T16:27:47Z","timestamp":1786724867000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/ijpm.ijpm_511_23"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,8]]},"references-count":19,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.4103\/ijpm.ijpm_511_23","relation":{},"ISSN":["0377-4929","0974-5130"],"issn-type":[{"value":"0377-4929","type":"print"},{"value":"0974-5130","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,8]]},"assertion":[{"value":"2023-06-25","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-06","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}